Renal Vein Thrombosis Suggestive of Extramembranous Glomerulonephritis Associated with Sjögren’s Syndrome (Case Report)

Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.

SIL1基因变异所致常染色体隐性Marinesco-Sj?gren综合征2例

Marinesco-Sj gren综合征(MSS)是一种罕见的常染色体隐性遗传病,以小脑共济失调、早发型白内障、慢性肌病、不同程度的智力残疾和运动发育迟缓为特征。患者还可表现出身材矮小、促性腺激素过低和肌肉无力导致的骨骼畸形等症状。本文报道2例表现为全面发育迟缓的MSS患儿临床与分子诊断过程,分别检出SIL1基因复合杂合致病变异c.109delG(p.Glu37Serfs*4)、意义未明变异c.353G>C(p.Arg118Thr)和c.443delA(p.Lys148Argfs*10)、可能致病变异c.707A>G(p.Asn236Ser)。明确分子诊断后,予以遗传咨询,评估患儿父母再生育风险。本文通过典型病例报道及既往文献回顾,以期提高临床医生对该疾病的认识,并为该病的诊断提供借鉴。

Role of ranulas in early diagnosis of Sjögren’s syndrome: A case report

BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.

Celiac disease and Sjögren’s syndrome:A case report and review of literature

BACKGROUND Celiac disease(CD)is a systemic,chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals,with a prevalence of 1%worldwide.Sjogren's syndrome(SS)is also a systemic autoimmune disease,mainly characterized by ocular and oral sicca symptoms and signs.Sharing a common genetic background,CD and SS are known associated autoimmune diseases,but currently available guidelines are not reporting it.CASE SUMMARY We report the case of a 39-year-old woman,who was in the care of her rheumatologist for 2 years with SS.On routine follow-up she was found to have iron deficiency,without anemia.She had no gastrointestinal complaints and denied any obvious source of blood loss.IgA tissue transglutaminase antibodies were positive and endoscopy with duodenal biopsies revealed crypt hyperplasia and villous atrophy.A diagnosis of CD was set and gluten-free diet was recommended.CONCLUSION We present a review of existing data in the literature regarding the association of the two diseases,summarizing prevalence studies of CD in SS patients and the other way around.Screening recommendations and future research perspectives are also discussed,highlighting clinically relevant unanswered questions with respect to the association of CD with SS.

Iguratimod in treatment of primary Sjögren’s syndrome concomitant with autoimmune hemolytic anemia:A case report

BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.

Peripheral Neuropathies Revealing Gougerot-Sjögren’s Syndrome: Description of 3 Cases

Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.

Sjögren’s Syndrome Revealed by Obstructive Renal Failure: A Case Report and Review of the Literature

Introduction: Primary Sjögren’s syndrome (SS) is the most common connective tissue disease after rheumatoid arthritis and affects mostly women between 30 and 40 years of age with an estimated prevalence between 0.1% and 0.6%. This observation illustrates an incidental finding of a case of SS in a young female patient in a context of obstructive renal failure (ARF) due to uterine fibroids. Observation: This was a 31-year-old woman hospitalized for anuric AKI (Acute Kidney Injury) with a creatinine level of 1247 μmol/l. Her history included sickle cell disease A/C and an unoperated uterine fibroid diagnosed 3 years ago. Approximately 2 months before her admission, her symptomatology was made of dizziness, physical asthenia, vomiting, poly-arthralgia, morning rash, pollakiuria and oral dryness. Abdominal examination showed a painless transverse mass in the pelvis. Biological examination showed a CRP (C-reactive protein) level of 488 mg/l. The cytobacteriological examination of the urine was normal and the proteinuria was 1.35 g/24 hours. The CT scan showed kidneys measuring 110 mm on the right and 113 mm on the left associated with bilateral pyelo-caliceal dilatation on a large polymyomatous uterus of interstitial and submucosal type. Immunologically, the anti-nuclear factor, the rheumatoid factor and the anti-SSA antibodies were positive. The resumption of the interrogation within the framework of the research of the subjective dry syndrome to find a notion of intermittent xerophthalmia 4 months ago. The Schirmer test was positive in the left eye. The initial management consisted of a polymyomectomy after 3 sessions of hemodialysis. Background treatment combining prednisone 5 mg/day and methotrexate 20 mg/week was started in parallel with the use of artificial tears. The evolution after twelve (12) months of treatment was favorable with a complete disappearance of the signs dry syndrome and full recovery of renal function. Conclusion: SS can have an insidious evolution and remain stable for many years, hence its fortuitous discovery in this case of obstructive ARF on uterine fibroid. In this context we insist on the interest of the immunological assessment in a patient in period of genital activity with a significant proteinuria and non-specific extrarenal signs.

AA Amyloidosis Secondary to Primary Sjögren Syndrome: Can It Be Developed without Chronic Inflammation?

Background: The association of primary Sjögren syndrome (PSS) and AA amyloidosis is a rare occurrence. Objective: To describe the phenotype of patients with this association through our two cases and a literature review. Materials and methods: A report of two cases of AA amyloidosis complicating primary Sjögren syndrome with a literature review. Results: Eight patients of Primary Sjögren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. Conclusion: The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.

Fas、FasL在Sjgren综合征涎腺组织中的表达及意义

目的 观察Sj gren综合征 (Sj gren’ssyndrome,SS)涎腺组织和正常涎腺组织中凋亡相关蛋白Fas、FasL的表达情况 ,探讨SS涎腺组织中细胞凋亡的途径。方法 采用SP免疫组织化学法 ,检测 2 3例SS涎腺组织和 16例正常涎腺组织中Fas、FasL的表达情况。结果 在SS腺泡上皮细胞中 ,Fas、FasL的表达均高于正常组 ,有显著性差异 (P <0 .0 0 5 ) ;两组导管上皮细胞中 ,Fas、FasL的表达均无显著性差异 (P >0 .0 5 )。结论 在SS涎腺组织中Fas、FasL的表达升高。SS涎腺上皮细胞在Fas/FasL介导下过度凋亡 。

Sjgren综合征涎腺组织中雌、雄激素受体的表达

目的 :探讨Sj gren综合征 (Sj gren’ssyndrome ,SS)与性激素的关系 ,以期为临床开展内分泌治疗提供理论依据。方法 :采用免疫组织化学法 ,检测 2 8例SS涎腺组织和 19例正常涎腺组织中雌激素受体 (ER)、雄激素受体 (AR)的表达情况。结果 :正常组与SS组ER的阳性率分别为 5 7.89%和 75 .0 0 % ,无显著性差异(P >0 .0 5 ) ;AR的阳性率分别为 84.2 1%和 5 0 .0 0 % ,有显著性差异 (P <0 .0 5 ) ;ER和AR主要位于腺泡和导管上皮细胞胞核内 ,而淋巴细胞仅偶见染色 ;SS唇腺、腮腺、颌下腺、舌下腺组织中 ,二者都为弱阳性到阳性染色 ,表达情况未见明显差异 (P >0 .0 5 )。结论 :SS涎腺病变与局部雄激素作用降低或丧失有关 ,雌、雄激素通过相应受体直接作用于涎腺上皮细胞 。

腮腺造影唇腺活检对Sjgren综合征的诊断价值

对100例综合征患者进行腮腺造影及唇腺活检、组织病理学检查，87例患者显示腮腺末梢导管扩张性改变；90例显示局灶性淋巴细胞浸润，符合郑麟蕃氏Ⅱ级，59例符合Chisholm4级。结果提示了疾病中两种腺体损害的一致性，也证实了损害的不均衡性。本研究提示了一种联合观察腮腺造影和唇腺活检结果诊断涎腺损害的新方法。

唾液钠、钾离子浓度和单位时间的总量及pH值变化与Sjgren综合征的关系

【目的】测定舍格伦综合征 (Sj grensyndrome,SS)患者唾液钠 (Na+ )、钾离子 (K+ )浓度和单位时间的总量及pH变化并探讨其与SS之间的关系。【方法】分组 :①正常对照组 (A组 ,n =30 ) ,风湿免疫组病人分为SS组 (B组 ,n =30 )和非SS组 (C组 ,n =2 4 ) ,单纯性口干组 (D组 ,n =15 ) ,共 4组。②采集各组唾液标本 ,应用离子选择电极电位测定分析法测定其Na+ 、K+ ,并对单位时间分泌总量进行观察 ,测pH值。③分别用t检验和单因素方差分析进行组间比较。【结果】B组Na+ 明显高于其他三组 (P <0 .0 0 1) ;B组K+ 虽高于A组 (P <0 .0 1) ,但与其他两组无显著差异。Na+ 总量B组与其他三组之间差异无显著性 ,但是C组和D组则低于A组 (P <0 .0 1) ;B组、C组、D组的Na+ 总量明显低于A组 (P <0 .0 1) ,B组与C组比较显著降低 (P <0 .0 0 1)。【结论】SS主要损害外分泌腺 ,因涎腺受累而导致唾液电解质浓度变化 ,这一现象可作为疾病的判定指标之一 ,对其诊断及与其他免疫疾病的鉴别诊断有一定价值。

Sjgren综合征涎腺组织中凋亡相关基因免疫组化分析

目的: 探讨凋亡相关基因bcl 2、bax、fas、fasL在Sj gren综合征(Sj grensyndrome, SS)涎腺组织中的表达及其在SS病变发生、发展中的作用。方法:采用SP免疫组化法,检测 16例SS涎腺组织和 10例正常涎腺组织中Bcl 2、Bax、Fas、FasL的表达情况。结果: Bcl 2在SS腺泡和导管上皮细胞的表达较正常组显著降低,而Bax表达明显增加;Fas、FasL在SS腺泡上皮细胞中的表达均高于正常组,而在导管上皮细胞中的表达均无显著性差异。结论:Bcl 2、Bax、Fas、FasL在SS涎腺组织中的表达发生异常,使得SS涎腺上皮细胞过度凋亡,造成了腺体结构的破坏和分泌功能的丧失;而浸润性淋巴细胞的凋亡被抑制,造成淋巴细胞聚集。

Sjgren综合征中T细胞亚群值的测定

目的：研究Ｓｊｏｇｒｅｎ综合征中Ｔ细胞亚群和免疫球蛋白的变化。方法：应用单克隆抗体技术检测Ｔ细胞亚群，用单向免疫扩散法检测ＩｇＡ、ＩｇＧ、ＩｇＭ结果：Ｓｊｏｇｒｅｎ综合征患者外周血中 ＣＤ４降低（Ｐ＜０．０５）、ＣＤ８升高（Ｐ＜０．０５），其程度与病情发展相一致，严重者ＣＤ４／ＣＤ８倒置。ＩｇＡ、ＩｇＧ、ＩｇＭ均升高（Ｐ＜０．０５），尤以ＩｇＧ显著（Ｐ＜０．０１）。结论：Ｓｊｏｇｒｅ综合征中存在免疫调节异常。

Sjgren综合征涎腺上皮细胞凋亡相关基因Bcl-2、Bax表达的研究

目的探讨凋亡相关基因Bcl-2、Bax在Sjgren综合征(Sjgren’ssyndrome,SS)涎腺上皮细胞中的表达及其作用机制。方法采用免疫组化SP法,检测22例SS涎腺组织和10例正常涎腺组织中Bcl-2、Bax的表达。结果SS组腺泡细胞Bcl-2阳性率为45.45%,显著低于正常组(P<0.05);导管上皮细胞的阳性率与正常组无显著性差异,但是染色强度却显著降低(P<0.05)。相反,SS组腺泡细胞中Bax阳性率为81.82%,显著高于正常组(P<0.05);导管上皮细胞的阳性率与正常组无显著性差异,但是染色强度却显著增强(P<0.05)。结论SS涎腺组织中Bcl-2表达减少,而Bax表达增加,使上皮细胞过度凋亡,导致涎腺结构破坏及分泌功能丧失。

Sjgren’s综合征所致干眼动物模型的研究进展

随着基因敲出鼠模型的出现及分子遗传学和免疫学等学科的发展,人们对Sjgren’s综合征(Sjgren’ssyndrome,SS)所致干眼的研究逐渐深入。近年来,许多SS所致干眼模型逐渐建立。这些模型研究了炎症反应、免疫机制、基因等因素在干眼发病中的重要作用。本文就国内外所建立的SS干眼模型的研究进展做一综述。

SIL1基因新发位点突变导致的常染色体隐性遗传性Marinesco-Sjogren综合征1例报告

Marinesco-Sjogren综合征(MSS;OMIM No.248800),又称为遗传性共济失调-侏儒-智力缺陷综合征,是一种罕见的常染色体隐性遗传性共济失调综合征,主要表现为先天性白内障、小脑共济失调、肌张力减退引起的进行性肌无力和精神运动发育迟缓。MSS患者还可以观察到其他次要特征,如身材矮小、高促性腺激素性性腺功能减退和肌肉无力导致的肌肉萎缩、骨骼畸形。

Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren’s syndrome

Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.

SHED-derived exosomes ameliorate hyposalivation caused by Sjögren’s syndrome via Akt/GSK-3b/Slug-mediated ZO-1 expression

Background:Sjögren’s syndrome(SS)is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations.The treatment is still challenging.This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth(SHED-exos)in sialadenitis caused by SS.Methods:SHED-exos were administered to the submandibular glands(SMGs)of 14-week-old non-obese diabetic(NOD)mice,an animal model of the clinical phase of SS,by local injection or intraductal infusion.The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice.Protein expression was examined by western blot analysis.Exosomal microRNA(miRNAs)were identified by microarray analysis.Paracellular permeability was evaluated by transepithelial electrical resistance measurement.Results:SHED-exos were injected into the SMG of NOD mice and increased saliva secretion.The injected SHED-exos were taken up by glandular epithelial cells,and further increased paracellular permeability mediated by zonula occluden-1(ZO-1).A total of 180 exosomal miRNAs were identified from SHED-exos,and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway might play an important role.SHED-exos treatment down-regulated phospho-Akt(p-Akt)/Akt,phospho-glycogen synthase kinase 3b(p-GSK-3b)/GSK-3b,and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells.Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1,a PI3K agonist.Slug bound to the ZO-1 promoter and suppressed its expression.For safer and more effective clinical application,SHED-exos were intraductally infused into the SMGs of NOD mice,and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt,p-GSK-3b/GSK-3b,and Slug and increased ZO-1 expression.Conclusion:Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3b/Slug pathway-mediated ZO-1 expression.

合并胎儿心脏病变的抗SSA抗体阳性孕妇的临床及实验室特征

目的:探究合并胎儿心脏病变的抗干燥综合征相关抗原A(Sj9gren’s-syndrome-related antigen A,SSA)抗体阳性孕妇的临床表现、实验室指征及药物特征。方法:在2013年1月至2023年7月于北京大学人民医院就诊且最终确诊自身免疫病的孕妇中,选择抗SSA抗体阳性且超声确诊胎儿心脏病变的患者作为病变组,抗SSA抗体阳性且超声检查无胎儿心脏病变的患者作为对照组,收集两组患者的临床、实验室及用药信息,比较组间基线数据无差异后对其临床指标进行统计学分析。结果:合并胎儿心脏病变的抗SSA抗体阳性患者共11例,其中有先天性房室传导阻滞表现者共7例,是最常见的胎儿心脏病变类型。病变组患者孕前确诊自身免疫病的比例显著低于对照组(P=0.032),多因胎儿心脏病变首次进行相关免疫学检查。病变组患者孕期白细胞水平[(9.29±2.58)×10^(9)/L vs.(7.10±1.90)×10^(9)/L,t=3.052,P=0.004]、红细胞沉降率[49.50(48.00,51.00)mm/h vs.23.00(15.00,30.25)mm/h,Z=-2.251,P=0.024]、IgA水平[3.46(2.30,5.06)g/L vs.2.13(1.77,2.77)g/L,Z=-2.181,P=0.029]、抗核抗体(antinuclear antibody,ANA)滴度[1∶320(1∶160,1∶320)vs.1∶80(1∶40,1∶160),Z=-3.022,P=0.003]显著高于对照组。组间孕期合并SSB抗体阳性的比例(37.5%vs.7.7%,P=0.053)、羟氯喹使用剂量及起用时间差异均无统计学意义。病变组孕期使用激素的比例及剂量显著高于对照组(P<0.05),其中孕早期两组间差异无统计学意义,而孕中期、孕晚期病变组激素使用剂量显著高于对照组。结论:胎儿心脏病变是一种罕见但与抗SSA抗体阳性高度相关的胎儿畸形,孕期白细胞、红细胞沉降率、IgA水平及ANA滴度显著升高的患者胎儿心脏病变发生的风险更高。胎儿房室传导阻滞一旦发生便难以逆转,因此,预防和监测的重要性高于补救治疗。